This invention relates to dentifrice products and methods for remineralizing and/or mineralizing teeth. More particularly, this invention relates to fluoride-containing dentifrice products and methods of using same to achieve improved remineralization of subsurface carious lesions and/or mineralization of exposed dentinal tubules.
Dental caries, i.e., tooth decay, is a leading cause of tooth damage in humans. Dental caries begins with lesions of so-called "white spots", which are demineralized areas below the surface of intact dental enamel. Such subsurface lesions are formed before a cavity is detectable. If unchecked, surface enamel above a subsurface lesion eventually collapses, leading to cavitation and subsequent loss of tooth structure.
Dental caries is typically caused by the presence of acids in the oral cavity. This is because the primary component of the enamel and dentin in teeth is calcium hydroxyapatite, which, though highly insoluble at normal oral pHs, is relatively soluble in acid media. Thus, when a tooth is exposed to acids, e.g., acids formed during the glycolysis of sugar caused by various oral bacteria, carious lesions can form in the enamel and dentin of the tooth.
Compositions and methods for preventing or reducing dental caries are known in the art. Reference is made, for example, to U.S. Pat. Nos. 3,966,901 (Cullum et al.): 4,714,608 (Rolla); 4,233,288 (Cornell); 5,129,905 and 5,407,031 (both to Constantz); 4,075,317 (Mitchell); and 2,700,012 and 2,627,493 (both to Merckel et al.).
Although it is desirable to prevent caries from spreading, it is also desirable to restore the carious tooth to its original state. Restoration of a carious tooth to its original state involves the process of remineralization. The object of remineralization is to deposit hydroxyapatite in the carious lesion such that the dental enamel incorporates the hydroxyapatite into its structure at the point of lesion. Thus, remineralization not only prevents further tooth decay but also restores the tooth to its original state.
Compositions and methods which use remineralization to retard or arrest dental caries are known in the art. Reference is made, for example, to U.S. Pat. Nos. 4,080,440 (Digiulio et al); 4,177,258, 4,183,915 and 4,348,381 (Gaffar et al); 4,083,955 (Grabenstetter et al); 4,397,837 (Raaf et al); 4,606,912 (Rudy et al.); 3,679,360 (Rubin et al.); 5,037,639; 5,268,167; 5,437,857; 5,427,768; and 5,460,803 (all to Tung); and 5,605,677 (Schumann et al). Reference is also made to U.S. Pat. Nos. 5,603,922 (Winston et al.); 5,605,675 (Usen et al.); and 5,571,502 (Winston et al.), and to commonly assigned U.S. Pat. No. 5,645,853.
U.S. Pat. No. 4,080,440 (Digiulio et al) discloses a method for remineralizing tooth enamel involving forming a metastable mixture having a low pH (between 2.5 and 4.0) by mixing a solution containing a soluble calcium salt and preferably a soluble salt of a heavy metal or magnesium with a solution containing a soluble phosphate salt and preferably a soluble fluoride salt, and then applying the metastable mixture to the tooth surface. A significant disadvantage of the use of metastable solutions is that the relatively low pH might demineralize the dental enamel and/or injure other tissue.
U.S. Pat. Nos. 4,177,258, 4,183,915 and 4,348,381 (Gaffar et al) disclose a remineralizing solution containing supersaturated concentrations of calcium ions, phosphate ions and a fluoride source stabilized by the present of an antinucleating agent such as diamine tetramethylenephosphonic acid, ethylenediamine tetramethylenephosphonic acid and 2-phosphonobutane-tricarboxylic acid-1,2,4, or the water-soluble salts thereof. This solution is preferably adjusted to the neutral pH range where the solution is alleged to most effectively remineralize subsurface lesions. Even though the antinucleating agent would be expected to stabilize the solution, equilibrium of the supersaturated concentrations is still found difficult to maintain and avoid precipitation of hydroxyapatite and changes in the pH of the solution.
U.S. Pat. Nos. 4,083,955 (Grabenstetter et al) and 4,397,837 (Raaf et al) disclose a process for remineralizing demineralized enamel by the consecutive treatment of tooth surfaces with separate solutions containing calcium ions and phosphate ions. In this process, the solution containing the calcium ions may further contain heavy metal ions or magnesium ions, while the solution containing the phosphate ions may also contain fluoride ions. By sequentially applying calcium and phosphate ions to the tooth surface, high concentrations of the ions are able to penetrate into lesions in solution form, where the ions precipitate as a calcium phosphate salt when ions from the second treatment solution diffuse in. While apparently successful, this method involves the inconvenience of a plurality of sequential applications, which can also be time consuming.
U.S. Pat. Nos. 4,606,912 and 4,610,873 (Rudy et al.) teach methods of making clear aqueous mouthwash solutions which totally prevent formation of calcium phosphate crystals, e.g., hydroxyapatite. The solutions are capable of remineralizing lesions in teeth and are prepared by initially forming a solution containing a source of calcium ions and a chelating agent for calcium ions, causing the chelation of at least 50% of the calcium ions and subsequently adding a source of phosphate ions to the aqueous solution. Here too, while somewhat effective, the addition and necessary control of the amount of chelating agent makes the concept impractical.
U.S. Pat. No. 3,679,360 to Rubin et al. discloses a remineralization method the purpose of which is to deposit calcium phosphate from a gel medium onto the surface of a tooth. This method of remineralization has several disadvantages. For example, in the Rubin et al. method, remineralization occurs only on the surface of a tooth whereas the initial cause of dental caries is subsurface demineralization. Furthermore, in the Rubin et al. method, the surface on which apatite growth is desired must be prepared (as by roughening), and the tooth and coatings must be covered by a suitable cap for several days while the mineralization of the tooth surface occurs.
U.S. Pat. Nos. 5,037,639; 5,268,167; 5,437,857; 5,427,768; and 5,460,803 (all to Tung) teach the use of amorphous calcium compounds such as amorphous calcium phosphate (ACP), amorphous calcium phosphate fluoride (ACPF) and amorphous calcium carbonate phosphate (ACCP) for use in remineralizing teeth. These amorphous compounds or solutions which form the amorphous compounds when applied either onto or into dental tissue prevent and/or repair dental weaknesses such as dental caries, exposed roots and dentin sensitivity. The compounds are claimed to have high solubilities, fast formation rates and fast conversion rates (to apatite). In the Tung patents, remineralization is accomplished by bringing the amorphous compound into contact with the dental tissue. This can be done directly, i.e., putting an amorphous compound directly on the tooth, or indirectly through a carrier, i.e., incorporating the amorphous compound in a carrier such as a gel, a chewing gum, or a toothpaste and applying the carrier to the dental tissue. Once contact is established with the tooth, the amorphous calcium phosphate compounds will recrystallize to the less soluble apatite form in the lesion and reform the tooth. However, under conditions where amorphous calcium phosphate compounds are stable, the quantity of calcium and phosphate released is relatively low and, therefore, remineralization is slower than desirable.
The aforementioned patents to Tung also teach the use of two-part solutions wherein a first part contains phosphate salt(s) and a second part contains calcium salts(s), wherein either the first part or the second part further contains carbonate salt(s). In addition, the Tung patents teach solutions formed by dissolving in water a solid powder containing calcium salt(s). These solutions are salt(s), and carbonate salt(s). These solutions are then applied to dental tissue. The Tung patents further teach the use of non-carbonated solid powders containing mixtures of calcium salts and phosphate salts which can be applied directly to the tooth or dispersed in gel, chewing gum, or other non-aqueous medium such as toothpaste which is placed in contact with the tooth. The patents teach that these powders are easily dissolved in saliva and then reprecipitated as an amorphous calcium phosphate compound. However, the Tung patents do not disclose the pHs of aqueous solutions formed from the non-carbonated solid powders.
U.S. Pat. No. 5,605,677 (Schumann et al.) discloses a toothpaste containing polishes, fluorine compounds, humectants, binders, and water, wherein the toothpaste is characterized in that it contains a combination of silica and dicalcium phosphate dihydrate at a weight ratio of 10:1 to 1:1 as the polishing component. According to the Schumann et al. patent, the toothpaste taught therein restores the surfaces of teeth by providing controlled remineralization, particularly in scratch marks and dentinal canals. Such remineralization renders these areas substantially level, leaving the teeth with a smooth continuous surface. Schumann et al. also teaches that the toothpaste therein may further contain magnesium ions and/or fluorophosphate ions. Schumann et al. does not disclose the presence of a water-soluble calcium compound in the toothpaste therein. Moreover, Schumann et al. does not teach the use of the magnesium ions to inhibit premature formation of calcium fluoride. The failure of Schumann et al. to teach this use of the magnesium ions therein is significant for reasons give hereinbelow.
U.S. Pat. No. 5,603,922 (Winston et al.) discloses one-part and two-part products and methods of using same to remineralize subsurface lesions. The one-part and two-part products contain at least one water-soluble calcium salt, at least one water-soluble divalent metal salt wherein the divalent metal is other than calcium and at least one water-soluble phosphate salt. The divalent metal is preferably magnesium, strontium, tin or zinc. In the two-part products, the calcium and divalent metal salts are disposed in a first discrete component, and the phosphate salt(s) is disposed in a second discrete component. The two-part product may further contain a dispensing means for allowing the first and second components to be simultaneously dispensed from the product so as to permit the dispensed first and second components to simultaneously contact the tooth or teeth being treated. The aqueous solution formed by mixing the salts used in the one-part and two-part products has a pH of from about 4.0 to about 7.0.
U.S. Pat. No. 5,605,675 (Usen et al.) discloses a two-part product and method of using same for remineralizing dental enamel, wherein the product contains a first discrete component composed of at least one water-soluble calcium salt and a second discrete component composed of at least one water-soluble phosphate salt and at least one water-soluble fluoride salt. The first and second components are simultaneously dispensable from the product and each have a pH in water such that when the two components are mixed to form an aqueous mixed solution, the solution has a pH of from about 4.5 and 10.0.
Commonly assigned U.S. Pat. No. 5,645,853 is directed to a chewing gum product and method of using same to remineralize subsurface lesions in teeth, wherein the chewing gum product contains a water-soluble cationic portion composed of at least one water-soluble calcium salt and at least one water-soluble divalent metal salt other than calcium salt; a water-soluble anionic portion containing at least one water-soluble phosphate salt; and a gum base. The divalent metal is preferably magnesium, strontium, tin or zinc. During chewing of the product, the anionic and cationic portions are simultaneously released into the water and/or saliva so as to form a mixed aqueous solution having a pH of from about 4.0 to 7.0.
U.S. Pat. No. 5,571,502 (Winston et al.) is directed to one-part, non-aqueous products and methods of using same to remineralize subsurface lesions, wherein the products contain at least one water-soluble calcium slat; at least one water-soluble phosphate salt; either a stabilizer or a hydrophilic, non-aqueous, water-soluble vehicle; and, optionally, at least one water-soluble fluoride salt. When the components are mixed with water or saliva to form an aqueous mixed solution, the solution has a pH of from about 4.5 to about 10.0.
Each of the products disclosed in the foregoing applications contains at least one water-soluble inorganic orthophosphate salt. For reasons discussed hereinbelow, it would be desirable to provide remineralizing/mineralizing dentifrice products which are substantially free of water-soluble inorganic orthophosphates.
Saliva itself helps protect teeth against demineralization and can slowly remineralize teeth which have become demineralized by acids. Because saliva is supersaturated with respect to calcium and phosphate ions, hydroxyapatite may be formed from substances occurring naturally in saliva. In the mouth, a natural equilibrium exists between the dissolution of hydroxyapatite from the teeth and the formation of hydroxyapatite on or in the teeth from the calcium and phosphate ions in the saliva. This equilibrium shifts continuously. If the equilibrium is such that hydroxyapatite is being dissolved, the result is demineralization and a carious condition. On the other hand, if the equilibrium is such that hydroxyapatite is being formed, remineralization occurs.
It is well known that fluoride ions can enhance the natural remineralization process, and this is one of the accepted mechanisms by which fluoride dentifrices protect against caries. Hydroxyapatite reacts with the fluoride ion and is thereby converted into fluoridated hydroxyapatite. Fluoridated hydroxyapatite is less soluble in an acid medium than is hydroxyapatite. Consequently, after a fluoride application, the tooth is better protected from the acid surges which initiate the caries process.
However, the efficacy of fluoride-containing dentifrices to remineralize teeth is limited by the modes levels of free calcium and inorganic orthophosphate ions present in saliva. The concentration of free calcium ions in saliva is especially limited. For example, the concentration of free calcium ions in parotid saliva varies from about 0.9 to about 1.5 millimoles per liter (36-60 parts per million (ppm)). On the other hand, the concentration of free inorganic orthophosphate ions in parotid saliva varies from about 3 to about 9 millimoles per liter (300-850 ppm) depending on the flow of the saliva. Since calcium hydroxyapatite and fluoroapatite contain a calcium-to-phosphate ion ratio of about 5:3, remineralization is most severely limited by the calcium ion levels in the saliva.
Thus, it would be desirable to provide a fluoride-containing dentifrice which could increase the concentration of free calcium cations available for use in the remineralization/mineralization process.
One way to increase the concentration of free calcium cations available for remineralization and/or mineralization would be to add a water-soluble or partially water-soluble calcium salt to the fluoride-containing dentifrice. However, the addition of a calcium compound to a fluoride-containing dentifrice is not a simple matter. Calcium ions react with fluoride ions to form insoluble calcium fluoride. The information of calcium fluoride removes free fluoride anions from the aqueous composition used to remineralize and/or mineralize the teeth. Thus, the premature formation of calcium fluoride in the composition used to treat the teeth inhibits the anticariogenic and remineralizing/mineralizing effects of the fluoride.
Compositions and methods designed to prevent the premature formation of calcium fluoride in dentifrice compositions are known in the art. Reference is made, for example, to U.S. Pat. Nos. 5,476,647 (Chow et al.); 4,283,385 (Dhabhar et al.); 4,923,683 (Sakuma et al.); 4,565,691 (Jackson); and 4,460,565 (Weststrate et al.).
The Chow et al. patent teaches a two-part dentifrice product containing a soluble calcium source in one part and a soluble fluoride source in the other part, wherein reaction between the calcium and fluoride sources is avoided by incorporating a soluble calcium-complexing anion into the calcium part.
The Dhabhar et al. patent teaches a dentifrice containing soluble fluoride and a calcium carbonate or calcium phosphate abrasive, wherein reaction between the fluoride and the abrasive is inhibited by the incorporation of an ethylenediaminetetraacetic acid or sodium salt thereof into the dentifrice.
The Sakuma et al. patent discloses that the reaction between a hydroxyapatite compound and a fluoride compound in a dentifrice composition can be prevented by either storing the hydroxyapatite and fluoride compounds in separate receptacles or by coating or encapsulating one or both of the hydroxyapatite and fluoride compounds.
In the Jackson patent, reaction between a water-soluble ionic fluoride and an ionic calcium-containing abrasive in a dentifrice composition is reduced or prevented by including in the dentifrice composition a water-soluble ionic agent containing the anionic counter ions of the ionic abrasive and metal cations capable of forming a water-soluble fluoride.
The Weststrate et al. patent teaches that a dentifrice composition containing two or more fluorine compounds, at least one soluble salt producing phosphate ions and at least one substance providing calcium ions, wherein inactivation of the fluoride and phosphate ions by the calcium ions is avoided by using specific calcium complexes as the source of calcium ions. Such calcium complexes include the calcium salts of organic acids, e.g., the calcium salts of citric acid, adipic acid, and tartaric acid. Calcium-enriched minerals such as calcium zeolite and calcium apofyllite are also suitable.
A drawback to the processes taught in the aforementioned patents to Chow et al., Dhabhar et al. Sakuma et al. and Weststrate et al., is that the chelating, sequestering or otherwise supplying of calcium in bound form, e.g., hydroxyapatite, ties up the calcium and reduces its availability for remineralization when applied to the teeth.
A drawback to the processes taught in the aforementioned patents to Jackson, and Schumann et al. is that providing the fluoride in complexed or bound form or even in the form of sodium monofluorophosphate reduces the availability of the fluoride for remineralization when applied to the teeth.
As stated previously herein, the amount of inorganic orthophosphate ions in parotid saliva is substantially grater than the amount of calcium ions in the saliva. Since hydroxyapatite contains a 5:3 ration of calcium ions to inorganic orthophosphate ions and further because it is desirable to avoid premature formation of calcium phosphate in the dentifrice aqueous composition used to remineralize and/or mineralize the teeth, it would be desirable to provide a fluoride-containing dentifrice product which increases the concentration of free calcium ions in the remineralizing/mineralizing aqueous composition used to treat the teeth but which does not increase the level of free inorganic orthophosphate ions already present in the saliva. In other words, it would be desirable to provide a dentifrice product which contains fluoride and calcium compounds but which is substantially free of water-soluble inorganic orthophosphates.
Dentifrice compositions containing calcium and fluoride compounds but free of water-soluble inorganic orthophosphate compounds are known in the art. Reference is made, for example, to U.S. Pat. Nos. 4,141,969 and 4,412,983 (both to Mitchell); 3,728,446 (Roberts et al.); 4,265,877 (Tenta); 4,983,379 (Schaeffer); 4,280,822 (Wason); 4,244,707 (Wason); 4,340,584 (Wason); and 5,045,305 (Clarkson et al.).
U.S. Pat. Nos. 4,141,969 and 4,412,983 to Mitchell disclose dental cream compositions containing a dental vehicle, synthetic precipitated silica essentially free of alumina, a fluorine-providing compound and a water-soluble or water-insoluble calcium salt. Phosphate compounds may be present but are not required. Optionally, the dental cream composition may further contain a metallic salt additive to provide metal ions in addition to the calcium ions. Magnesium salts, particularly water-soluble magnesium salts, such as magnesium chloride, are particularly desirable.
U.S. Pat. No. 3,728,446 to Roberts et al. teaches a speckled dentifrice gel composition containing a gel vehicle composed of an aqueous liquid, an alkali metal carboxymethyl cellulose gelling agent, colored particles of the water-insoluble salt of carboxymethyl cellulose and a polyvalent metal, and, optionally, a soluble fluoride compound. The polyvalent metal, which is provided as a water-soluble salt or water-soluble hydroxide, can be calcium, magnesium, strontium, barium, aluminum, gallium, germanium, tin, lead, iron, nickel, zinc, or cadmium. The composition may further contain a polishing agent such as, e.g., magnesium carbonate, calcium carbonate, dicalcium phosphate, tricalcium phosphate, insoluble sodium metaphosphate, calcium pyrophosphate, calcium sulfate and mixture thereof.
U.S. Pat. No. 4,265,877 to Tenta is directed to a chewing gum composition containing a chewing gum base having distributed therein a mixture of sodium fluoride and calcium carbonate in the form of oyster shell. The oyster shell consists of about 97% of calcium carbonate and about 3% of a mixture of trace elements such as magnesium, silicon, manganese, iron, aluminum, copper, sodium, strontium, potassium and zinc.
U.S. Pat. No. 4,983,379 to Schaeffer discloses a dental preparation containing a hydrogen peroxide-containing gel component and a sodium bicarbonate-containing paste component, the gel and paste components being separately stored but capable of being simultaneously dispensed from the package in which they are contained. The paste component may further contain a fluorine compound and cleansing agents such as calcium sulfate, calcium phosphate, calcium carbonate, magnesium carbonate, magnesium silicate, and mixtures of the foregoing. The paste component may also contain a polishing/stabilizing agent such as magnesium oxide. U.S. Pat. Nos. 4,280,822; 4,244,707; and 4,340,584 to Wason disclose dentifrice compositions containing a fluoride-containing therapeutic agent, a polishing agent, a liquid phase, and alkaline earth metal ions. The alkaline earth metal may be calcium, magnesium or strontium, but is preferably calcium. The alkaline earth metal compound is water-soluble and includes the nitrates, oxides, hydroxides and chlorides. The polishing agent may be e.g., dicalcium phosphate, anhydrous dicalcium phosphate, tricalcium phosphate, thermally converted dicalcium phosphate, and insoluble sodium metaphosphate.
U.S. Pat. No. 5,045,305 to Clarkson et al. teaches an oral hygiene product for inhibiting caries, which contains a first composition containing an aqueous solution of calcium ions and a second composition containing an aqueous solution of fluoride ions, wherein the first and second compositions are such that when mixed, rapid precipitation of calcium fluoride occurs. The oral hygiene product maintains a low fluoride ion concentration in the mouth for longer periods than conventional products by the rapid precipitation of calcium fluoride either in the mouth or immediately prior to use. A delivery system providing for physical separation of the two compositions and for simultaneous or sequential delivery of the compositions may also be used.
Although the foregoing patents teach dentifrice compositions containing calcium and fluoride compounds but which are free of water-soluble inorganic orthophosphate compounds, none of the patents teaches or suggests the use or usefulness of the dentifrice product disclosed therein for effecting remineralization and/or mineralization, particularly subsurface remineralization and/or mineralization.
It is desirable to provide dentifrice compositions containing calcium and fluoride compounds and free of water-soluble inorganic orthophosphate compounds, wherein such dentifrice compositions are capable of providing remineralization of subsurface lesions and/or mineralization of exposed dentinal tubules.
Accordingly, it is a primary object of this invention to provide dentifrice products and methods which are capable of providing faster remineralization of subsurface lesions and faster mineralization of exposed dentinal tubules.
A further object of this invention is to provide a fluoride-containing dentifrice product for remineralizing subsurface lesions and/or mineralizing exposed dentinal tubules, wherein the dentifrice product further contains a source of calcium cations and is capable of adding calcium cations to the aqueous saliva composition used to treat the teeth.
A still further object of this invention is to provide a dentifrice product for remineralizing subsurface lesions and/or mineralizing exposed dentinal tubules, wherein the dentifrice product contains a source of fluoride ions and a source of calcium ions, wherein reaction between the fluoride and calcium sources to form calcium fluoride in the aqueous saliva composition used to treat the teeth is substantially delayed for a period of several minutes.
Another object of this invention is to provide a dentifrice product for remineralizing subsurface lesions and/or mineralizing exposed dentinal tubules, wherein the dentifrice product contains a source of fluoride ions and a source of calcium ions but is substantially free of soluble inorganic orthophosphates.
Yet another object of this invention is to provide a product which has the foregoing characteristics and which is easily usable by the consumer and not differing significantly, in flavor and appearance, form customary dental cosmetics.
A further object of this invention is to provide a method for remineralizing subsurface lesions and/or mineralizing exposed dentinal tubules by means of a product having the aforementioned characteristics.
These and other objects which are achieved according to the present invention can be readily discerned from the following description.